This project on human immunogenetics of the major histocompatibility complex is an integrated investigation of immunological, genetic and biochemical aspects of the HLA complex and closely linked genes. The overall objectives for this project are to obtain a better understanding of the genetic factors responsible for allograft reactions, to identify the immunological mechanisms involved in such reactions and to understand the relationship between the HLA complex and genetic factors predisposing to diseases. The studies are divided into four projects. (1) Cell surface phenotype and function of human alloactivated lymphocytes. This project utilizes the techniques of T-lymphocyte cloning for the analysis of lymphocyte diversity. (2) In vitro production by human B lymphocytes of human monoclonal antibodies detecting cell surface antibodies is being investigated. (3) Serological, biochemical and genetic analysis of the human equivalent of the thymus-leukemia (TL) antigen will be undertaken and compared with the murine counterparts. (4) The relationship between a disease-causing gene and HLA will be investigated using congenital adrenal hyperplasia due to 21-hydroxylase deficiency as a model. This project utilizes molecular genetic tools for the analysis of the genes in the HLA region. During the last year, we have described the cell surface phenotype of cytotoxic T-cell clones which recognize Class I and Class II HLA antigens and have investigated the relationship between these T-cell differentiation antigens and the target antigens. Techniques have been developed for the in vitro production of human monoclonal antibodies detecting cell surface antigens. Biochemical characterization of at least two different forms of the human TL antigens has been performed. Finally, we have obtained preliminary evidence for the identification of the structural gene coding for adrenal 21-hydroxylation.